HIV (Human Immunodeficiency Virus (type 1)) belonging to retrovirus is a causative virus of AIDS (Acquired Immunodeficiency Syndrome).
HIV targets CD4 positive cell groups such as helper T cell, macrophage and dendritic cell and destroys these immunocompetent cells to cause immunodeficiency.
Accordingly, a pharmaceutical agent that eradicates HIV in a living organism or suppresses its growth is effective for the treatment or prophylaxis of AIDS.
HIV possesses a bimolecular RNA gene in a shell, and which is covered with an envelope protein. The RNA codes for several enzymes (protease, reverse transcriptase, integrase etc.) characteristic of the virus and the like, and has translated reverse transcriptase and integrase in the core, as well as protease inside and outside the core.
HIV contacts and invades a host cell, causes uncoating, and releases a complex of RNA and integrase, and the like into the cytoplasm. From the RNA, DNA is transcribed by reverse transcriptase, and a full length double stranded DNA is produced. The DNA moves into the core of the host cell and is incorporated by integrase into the DNA of the host cell. The incorporated DNA is converted to an mRNA by polymerase of the host cell, from which mRNA various proteins necessary for forming a virus are synthesized by HIV protease and the like, and a virus particle is finally formed, which then undergoes budding and its release.
These virus specific enzymes are considered to be essential for the growth of HIV. These enzymes are drawing attention as the target of the development of antiviral agents, and several anti-HIV agents have been already developed.
For example, zidovudine, didanosine, lamivudine and the like have been already on the market as reverse transcriptase inhibitors, and indinavir, nelfinavir and the like as protease inhibitors.
In addition, a multiple drug combination therapy concurrently using these pharmaceutical agents has been employed. For example, a combined use of two reverse transcriptase inhibitors (zidovudine and didanosine), and a combined use of three agents of reverse transcriptase inhibitors (zidovudine and lamivudine) and a protease inhibitor (nelfinavir) have been clinically applied. Such multiple drug combination therapy is becoming a mainstream of AIDS therapy (Folia Pharmacologica Japonica, 118, 131–134, 2001).
However, some of these pharmaceutical agents are known to HIV cause side effects such as liver function failure, central nervous disorders (e.g., vertigo), and the like. In addition, acquisition of resistance to a pharmaceutical agent causes a problem. Even worse, emergence of an HIV that shows multiple drug resistance in a multiple drug combination therapy has been known.
Under the circumstances, a further development of a novel pharmaceutical agent, particularly a development of an anti-HIV agent based on a new mechanism, has been desired, wherein a development of an anti-HIV agent having an integrase inhibitory activity is-expected, because an integrase characteristic of retrovirus is an essential enzyme for the growth of HIV.
Nevertheless, an effective integrase inhibitor has not been found as yet.
Known compounds comparatively similar to the anti-HIV agent of the present invention are described in the following.
WO01/96283 describes, as an anti-HIV agent having an integrase inhibitory activity, the following compound [A] (see WO01/96283, p. 176, compound 70).

WO03/016266 describes the following compound [B] and the like having an integrase inhibitory activity (see WO03/016266, p. 159, Example Nos. 3–17).

WO01/95905 describes the following compound [C] and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO01/95905, p. 109, Example E-2).

In addition, WO03/047564 describes the following compound [D] and the like, as an anti-HIV agent having an integrase inhibitory activity (see WO03/047564, p. 73, Example 11).

Moreover, WO02/30930 and WO02/55079 describe, as an anti-HIV agent having an integrase inhibitory activity, the following compounds [E], [F] and the like, respectively (see WO02/30930, p. 171, Example 1; WO02/55079, p. 79, Example 1). WO02/30426, WO02/30931 and WO02/36734 also disclose similar compounds.

In addition, WO03/031413 describes, as an anti-HIV agent having an integrase inhibitory activity, the following compound [G] and the like (see WO03/031413, p. 21, compound 8).

Moreover, WO03/035076 and WO03/035077 describe, as an anti-HIV agent having an integrase inhibitory activity, the following compounds [H], [i] and the like (WO03/035076, p. 188, Example 1; WO03/035077, p. 146, Example 22).

However, these publications do not disclose nitrogen-containing fused ring compound encompassed in the present invention, or a description suggestive thereof.
Furthermore, WO2004/24078 describe, as an anti-HIV agent having an integrase inhibitory activity, the following compound [J] and the like.

This publication describes the following formula as the formula (I) of claim 1 and a tautomer thereof. However, the compound described in this publication is clearly different from the compound of the present invention in that a hydroxyl group or a carbonyl group is essential at a position corresponding to the position of Ry1 for y2 in the formula [I] of the nitrogen-containing fused ring compound of the present invention. In addition, this publication does not suggest a compound free of a hydroxyl group or a carbonyl group at said position.

A production method of the compound of the formula (I) is disclosed in this publication from page 46 to page 113, but the production method concretely disclosed here cannot produce a nitrogen-containing fused ring compound encompassed in the present invention, and a concrete production method of this compound is not referred to at all.